Myosin Binding Protein-C Slow: An Intricate Subfamily of Proteins

Maegen A Ackermann,Aikaterini Kontrogianni-Konstantopoulos

doi:10.1155/2010/652065

Maegen A Ackermann, Aikaterini Kontrogianni-Konstantopoulos

Open Access

https://doi.org/10.1155/2010/652065

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Abstract

Myosin binding protein C (MyBP-C) consists of a family of thick filament associated proteins. Three isoforms of MyBP-C exist in striated muscles: cardiac, slow skeletal, and fast skeletal. To date, most studies have focused on the cardiac form, due to its direct involvement in the development of hypertrophic cardiomyopathy. Here we focus on the slow skeletal form, discuss past and current literature, and present evidence to support that: (i) MyBP-C slow comprises a subfamily of four proteins, resulting from complex alternative shuffling of the single MyBP-C slow gene, (ii) the four MyBP-C slow isoforms are expressed in variable amounts in different skeletal muscles, (iii) at least one MyBP-C slow isoform is preferentially found at the periphery of M-bands and (iv) the MyBP-C slow subfamily may play important roles in the assembly and stabilization of sarcomeric M- and A-bands and regulate the contractile properties of the actomyosin filaments.

Highlights

Myofibrils, the workhorses of skeletal muscle, consist of interdigitating thick and thin filaments, and their associated membrane systems [1]
Total RNA was isolated with Trizol reagent (Invitrogen, Carlsbad, CA) from postnatal day 1 (P1) rat skeletal myotubes cultured for seven days and from adult rat extensor digitorum longus (EDL), flexor digitorum brevis (FDB), tibialis anterior (TA), gastrocnemius, quadriceps, and soleus muscles
Four different Myosin binding protein C (MyBP-C) slow transcripts have been identified in human skeletal muscle referred to as variants 1–4 (Figure 1; accession numbers NM 002465, NM 206819, NM 206820, and NM 206821, respectively)

Summary

Introduction

Myofibrils, the workhorses of skeletal muscle, consist of interdigitating thick and thin filaments, and their associated membrane systems [1]. Myosin Binding Protein-C (MyBPC) comprises a family of accessory proteins that contributes to the assembly and stabilization of thick filaments, and regulates the formation of cross-bridges between myosin and actin by interacting directly with both filamentous systems (as reviewed in [3]). MyBP-C, originally termed C-protein for its location on SDS-PAGE as band C, was further characterized as a myosin binding protein of ∼140 kDa using a combination of biochemical methods, ranging from gel filtration, to ammonium sulfate fractionation and single molecule electron microscopy [4,5,6]. The location of MyBP-C at striped intervals within the C-zone of the A-band of skeletal muscle was first observed with Xray diffraction and immunoelectron microscopy [7], further supporting its association with the thick myosin filaments. Subsequent studies revealed that MyBP-C is arranged along the length of the A-band in 7–9 transverse stripes that are ∼43 nm apart, with ∼2–4 molecules of MyBP-C associating with each myosin cross-bridge [8,9,10,11]

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